Tuning the photoactivity of diazido Pt(IV) prodrugs with amino acid methyl esters
Year: 2025
Type: article
Abstract: Photoactive Pt(IV) complexes conjugated to amino acid methyl esters trans , trans , trans -[Pt(py) 2 (N 3 ) 2 (OH)(succinate-amino acid methyl ester)] (amino acid = L-leucine ( 1 ), glycine ( 2 ), L-tyrosine ( 3 ) and L-tryptophan ( 4 )) have been synthesised and characterised. Complexes 1 – 4 showed high dark stability, but were activated upon irradiation with blue light to generate azidyl and hydroxyl radicals and Pt(II) species. Interestingly, conjugated tryptophan in 4 quenched the formation of azidyl and hydroxyl radicals and Pt-guanosine 5′-monphosphate adducts, while the amino acids in complexes 1 – 3 showed no significant effects on the formation of their photoproducts. Improved photocytotoxicity but lower dark cellular Pt accumulation in A2780 human ovarian cancer cells were observed for 1 – 4 , with 50 % inhibition of cell viability (IC 50 ) values of 1.4–7.0 μM) compared with the parent complex FM-190 ( trans, trans, trans -[Pt(py) 2 (N 3 ) 2 (OH) 2 ]). Significant enhancement in Pt accumulation for 3 and 4 after irradiation probably contributes to their promising photocytotoxicity, especially for the tryptophan-conjugated complex 4 . Octahedral diazido Pt(IV) complexes with axial conjugation of amino acid methyl esters are non toxic to human ovarian cancer cells in the dark, but potently cytotoxic when irradiated with visible light. Remarkably, tryptophan conjugation quenches formation of azidyl and hydroxyl radicals and guanine binding. • Photoactive Pt(IV) complexes with high dark stability and promising photoactivity. • Conjugated tryptophan quenched the formation of radicals and Pt-GMP adducts. • Photocytotoxicity controllable by amino acid methyl ester conjugation. • Significant enhancement in cellular Pt accumulation after irradiation.
Authors: Huayun Shi, Peter J. Sadler
Institutions: Xiamen University, University of Warwick
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,220
OpenAlex ID: W4413237975